DK148443B - PROCEDURE FOR RACEMIZING OPTICALLY ACTIVE AMINES - Google Patents

Description

U8U3

The present invention relates to a particular method for racemizing optically active amines in the presence of an alkali metal catalyst.

The optically active amines which can be racemized by the method 5 of the invention can be represented by the general formula I

1 * 2

R-CH-ir I

nh 2 * 1 where C represents an asymmetric carbon atom, R represents C 1-6 alkyl, aralkyl of not more than 18 carbon atoms, or aryl of not more than 18 carbon atoms and R represents aryl of not more than 18 carbon atoms or alkoxycarbonyl of not more than 9 carbon atoms, wherein the aryl or aralkyl moiety optionally carries one or more C 1-6 alkyl or C 1-4 alkoxy groups on the 1 2 aromatic ring, with the proviso that R and R are always different from each other or R represents ethoxycarbonylmethyl, and R represents ethoxycarbonyl.

Optically active amines of the general formula I can be used as industrial chemicals, agricultural chemicals and the like. They can also be used as intermediates in the preparation of useful chemical substances. Furthermore, they can be used as cleavage agents to prepare (+) - trans-chrysanthemic acid (U.S. Patent No. 3,739,019).

Generally, these optically active amines of general formula I are prepared on an industrial scale in the form of racemic mixtures, which are then subjected to cleavage. After separation of the optical antibodies which are useful, the remaining undesirable antibodies are subjected to racemization and cleavage so as to obtain additional amounts of the optical antibodies useful. Thus, racemization is one of the valuable methods for preparing the optically active amines of the general formula I.

U.S. Patent No. 3,168,566 discloses a process for racemizing optically active α-phenylethylamine by heating at a temperature of from 60 ° C to the boiling point of the starting amine in the presence of an alkali metal. To achieve racemization in such a process, it is necessary to bring the temperature up to almost 200 ° C.

The most desirable result is obtained in the presence of metallic sodium.

However, the process described in the United States patent has a major drawback, namely that when it is adapted to a larger volume unit, the duration (i.e., the time for heating, reaction and cooling) of the metallic sodium's residence in the reaction mixture is extended, leading to degradation. of the amine and thus a yield loss.

In contrast, the process of the present invention is not carried out using a conventional alkali metal, but using an activated catalyst. Racemization can easily be achieved with high yields at low temperature (below 60 ° C). The catalyst used in the process of the invention is one which has a high surface area and increased activity and which yields results significantly different from those obtained with the use of a conventional alkali metal (cf. Experiment 1 below).

Swedish Patent Specification No. 379,756 relates to a method for racemizing optically active ο, β-alkyl-substituted phenylethylamine with a catalytic reduction catalyst (e.g., Ni, Pd, Rh, Re) in an inert gas or ammonia gas under heating.

In this process, the racemization temperature ranges from 100 ° C to the boiling point of the starting amine, preferably from 140 ° C to 150 ° C. Thus, the process requires an expensive precious metal catalyst and a high temperature.

In the process according to the invention, the racemization can be carried out smoothly at a much lower temperature in good yield, and no expensive catalyst is required, which makes the process according to the invention more advantageous than the process described in the Swedish egg egg publication.

U8443 3

As a result of a comprehensive study of the racemization of optically active amines of general formula I, it has now surprisingly been found that certain particular catalysts are very effective in racemizing the optically active amines and readily under room temperature conditions. give the racemic mixtures in quantitative yields.

Thus, the process of the invention for racemizing optically active α-amines of general formula I in the presence of an alkali metal catalyst is characterized in that the optically active amine is treated with a catalyst which is A) an alkali metal deposited on a solid support. B) an alkali metal dispersed in a liquid medium or C) an alkali metal alloy liquid at the process temperature, in an amount equal to 1 / 1000-1.5 moles per liter. mole of the optically active amine and at a temperature between -10 ° C and + 50 ° C until a sufficient amount of the optically active amine is racemized.

The invention will now be explained in more detail:

As the alkali metal catalyst, any metal of Group I of the periodic system can be used, e.g. lithium, sodium, potassium or rubidium, which has been given a form as catalyst A, B or C.

Catalyst A can be prepared by depositing the alkali metal on a solid support such as alumina, silica gel, aluminum silicate, magnesium silicate or activated carbon. Preferably, the solid support has a surface area of at least approx. 25 m per g, and a higher surface area is more effective. To prepare a suitable catalyst, the deposit 25 of the alkali metal on the solid support is carried out at a temperature which is above the melting point of the alkali metal, under an atmosphere of inert gas, e.g. nitrogen, helium or argon. In particular, when alumina is used as a solid support, a highly active catalyst can be obtained by depositing at a temperature of from 200 to 500 ° C.

The amount of alkali metal to be used is usually from 1 to 30% by weight, preferably from 4 to 20% by weight, based on the weight of the solid support. Catalysts of this type are known as catalysts which are effective in the isomerization of olefins such as butenes [J. Am.Chem.Soc., 82, 387 (1969)].

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Catalyst B can be prepared by dispersing the alkali metal in a liquid medium, e.g. toluene, xylene or a mineral oil. The suitable dispersing medium is inactive against the alkali metal and has a boiling point which is above the melting point of the alkali metal. To prepare a suitable catalyst, the alkali tablet is dispersed with stirring in the liquid medium at a temperature above the melting point of the alkali metal. The amount of alkali metal to be dispersed is usually from 20 to 60% by weight, based on the total weight of the alkali metal and liquid medium.

Catalyst C is an alkali metal alloy which is liquid under the process conditions, e.g. sodium potassium alloy. In the case of sodium-potassium alloy, e.g. an alloy containing 22-95% by weight of potassium has a melting point of less than 50 ° C, and an alloy containing 77% by weight of potassium has a melting point of -12 ° C. The racemization proceeds very rapidly by stirring the reaction mixture when the abovementioned alkali metal alloy is used as a catalyst at a reaction temperature in the range of approx. -10 ° C to approx. + 50 ° C.

The optically active amine for which the process of the invention can be used is one which is shown by the above general formula I wherein R is in the meaning of alkyl of not more than 8 carbon atoms, e.g. are methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl, in the sense aralkyl having not more than 18 carbon atoms, e.g. are benzyl, phenethyl, naphthylmethyl or naphthylethyl or, in the meaning of aryl, having a maximum of 18 carbon atoms, e.g. is phenyl or naphthyl, and R in the sense aryl having a maximum of 18 carbon atoms e.g. is phenyl or naphthyl, or in the sense alkoxycarbonyl having not more than 9 carbon atoms e.g. are methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl. Specific examples of the optically active amine of general formula I are α-phenylethylamine, o-phenylpropylamine, α- (p-tolyl) ethylamine, α- (1- or 2-naphthyl) ethylamine, α, β-diphenylethylamine , β ~ (ρ-, o- or m-tolyl) -cc-phenylethylamine, β- (ρ-, o- or m-ethylphenyl) -α-phenylethylamine, β- [ρ-, o- or m- (n- or iso-) propylphenyl] -α-phenylethylamine, β- [ρ-, o- or 35 m- (n-, iso- or tert .-) butylphenyl] -α-phenylethylamine, β-phenyl-α- (p-, o- or m-tolyl) ethylamine, β-phenyl-α-fp-, o- or m-ethylphen-U8U3 5-yDethylamine, 3-phenyl-α- [p-, o- or m- (n - or iso-) propylphenyl] -ethylamine, β-phenyl-ct-fp-, o- or m- (n-, iso- or tert-butylphenyl] ethylamine, β- (ρ-, o- or m-tolyl) -ct- (p-, o- or m-tolyl) ethylamine, β- (ρ-, o- or m-tolyl) -a- (p-, o- or m-ethylphenyl) ethyl -5 min, β- (ρ-, o- or m-tolyl) -o- [p-, o- or m- (n- or iso-) propyl-phenyl] ethylamine, β- (ρ-, o- or m-tolyl) -a- [p-, o- or m- (n-, iso- or tert-butylphenyl] ethylamine, β- (ρ-, o- or me) thylphenyl) ~ α- (p-, o- or m-ethylphenyl) ethylamine, β- (ρ-, o- or m-ethylphenyl) -a- (p-, o- or m-tolyDethylamine, β- ( ρ-, o- or m-ethylphenyl) -10 α- [p-, o- or m- (n- or iso-) propylphenyl] ethylamine, β- (ρ-, o- or m-ethylphenyl) -α [p-, o- or m- (n-, iso- or tert-butyl-phenyl] ethylamine, β- [ρ-, o- or m- (n- or iso-) propylphenyl] -a- ( p-, o- or m-tolyl) ethylamine, β- [ρ-, o- or m- (n- or iso-) propylphenyl] -a- (p-, o- or m-ethylphenyl) ethylamine, β - (ρ-, o- or 15 m- (n- or iso-) propylphenyl] -a- [p-, o- or m- (n- or iso-) propylphenyl] ethylamine, β- [ρ- , o- or m- (n- or iso-) propylphenyl] -a- [p-, o- or m- (n-, iso- or tert.-) butylphenyl] ethylamine, β- [ρ-, o- or m- (n-, iso- or tert -butylphenyl] -a- (p-, o- or m-tolyl) -ethylamine, β- [ρ-, o- or m- (n- or iso-) or tert .-) butylphenyl-β- (ρ-, o- or m-ethylphenyl) ethylamine, β- [ρ-, o- or m- (n-, iso- or tert.-) butylphenyl] -α [p-, o- or m- (n- or iso-) propyl-phenyl] ethylamine, β- [ρ-, o- or m- (n-, iso- or tert-butylphenyl) -a- [p-, o- or m- (n-, iso- or tert-butylphenyl) ] ethylamine, alanine methyl ester, alanine butyl ester, norvaline propyl ester, leucine ethyl ester, β-phenylalanine methyl ester, β-phenylalanine propyl ester and β-3,4-dimethoxyphenylalanethyl ester.

The optically active amine of general formula I may comprise the d-form and / or l-form in any ratio.

The racemization can be carried out chargeably or continuously. The optically active amine of the general formula I may be introduced alone or together with the catalyst in a reaction vessel where the racemization is carried out. If desired, it may be introduced successively or intermittently into the reaction vessel, depending on the course of the racemization.

U8443 6

The ratio of the catalyst to the optically active amine of the general formula I need not be critically observed. Thus, the catalyst can be used in such an amount that a suitable yield of the racemic mixture is obtained within a suitable reaction time. However, for economic reasons, the catalyst is used in an amount of 1 / 1000-1.5 mol, preferably 1 / 200-1 / 10 mol, per liter. moles of the optically active amine of the general formula I.

The reaction temperature of the process according to the invention must be in the range between -10 ° C and + 50 ° C for the successful execution of the racemization. When the reaction temperature is lower than -10 ° C, the racemization rate becomes too small for industrial purposes. When the temperature is higher than 50 ° C, the rate of racemization becomes greater, but the optically active amine of the general formula I and / or other undesirable side reactions may be decomposed.

The racemization can proceed quantitatively, although no solvent is present. If desired, any solvent which has no adverse effect on the course of racemization may be used. To safely achieve the racemization, the operation can be performed under an atmosphere of any inert gas. Furthermore, it is usually preferred to remove any residual water or moisture from the optically active amine of general formula I prior to contact with the catalyst.

The reaction time is more or less related to the amount of catalyst used and the reaction temperature used. The reaction time is usually shorter with a larger amount of the catalyst and a higher reaction temperature.

The course of racism can be monitored, e.g. by measuring the optical rotation at a particular concentration or by analyzing using gas chromatography.

When the reaction is complete, the product recovery can be carried out by conventional purification methods. Eg. after removal of the catalyst from the reaction mixture, the reaction mixture can be treated by distillation or chromatography. The purification can also be carried out by forming a salt of the resulting amine of general formula I with an acid. Since the racemization proceeds quantitatively, the reaction product can be of high purity even in cases where no purification procedure is used.

In the process of the invention, the racemization can be carried out quantitatively using a small amount of the catalyst under mild conditions. The method according to the invention is thus attractive from the point of view of operational, apparatus and economic considerations.

Practical and presently preferred embodiments of the method according to the invention are illustrated by the following examples:

Part I: This section gives examples of racemization using catalyst A. The catalysts used are prepared as follows:

Method a.

Into a 200 ml flask is placed 100 g of 200-300 mesh alumina particle calcined at 500 ° C for 2 hours and heated at 400 ° C under nitrogen atmosphere with stirring. After adding 10 g of metallic sodium at the same temperature as above, the resulting mixture is stirred for 1 hour to give a catalyst (i.e., an alkali metal deposited on a solid support).

Method b.

Proceeding as described in Method a, a catalyst is prepared from 100 g of alumina and 6 g of metallic potassium by heating at 200 ° C.

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Method c.

Proceeding as described in Method a, a catalyst is prepared from 100 g of alumina and 5 g of metallic potassium by heating at 200 ° C.

EXAMPLE 1 25 g of (+) - α- (1-naphthyl) ethylamine 20 ° C [a] D + 81.3 ° (without solvent) in 25 ml flask is placed under nitrogen atmosphere and 5 is added. 0 g of catalyst prepared as described under Method a. The resulting mixture is stirred at room temperature. The optical rotation of the reaction mixture is measured during the reaction time as shown in Table I.

Table I

2ø

Reaction time, 578 ° C = + (ethanol) hours 15 ____ 0 + 57.1 ° 1 + 30.4 ° 2 + 13.2 ° 3 + 4.6 ° 20 5 -1.9 °

After filtration of the catalyst, it is washed with toluene and the filtrate is concentrated and then distilled under reduced pressure to give 22.4 g of racemic α- (1-naphthyl) ethylamine. Boiling point 124-126 ° C / 2.0 mm Hg, n + = 1.6224.

EXAMPLE 29 In a 100 ml reaction vessel, put 20 g of (-) - α- (1-naphthyl) -20 ethylamine ([ot] + = -58.2 ° (without solvent)) and 30 g of dry toluene under nitrogen atmosphere. and 4.0 g of catalyst 5 prepared as described under Method b is added. The mixture is stirred for 4 hours at 30 ° C. After filtration of the catalyst, the filtrate is treated in the same manner as described in Example 1 to give 17.3 g of racemic α- (1-naphthyl) ethylamine. Boiling point 102-105 ° C / 0.3 mm Hg, 2.5 [ot] = -0.7 ° (without solvent).

EXAMPLE 3 Into a 100 ml flask, place 50 g of (+) - α-phenyl-n-propylamine 2.5 ([+] q = + 21.0 ° (without solvent)) under a nitrogen atmosphere and add 3, 0 g of catalyst prepared as described under Method a. The mixture is stirred for 7 hours at 25 ° C. After filtering off the catalyst, the filtrate is distilled under reduced pressure to give 46.3 g of racemic α-phenyl-n-propylamine. Boiling point 99-100 ° C / 16 2 5 mm Hg, [o] q = + 0.1 ° (without solvent).

EXAMPLE 4 2 In a 100 ml flask, place 50 g of (-) - α- (p-tolyl) ethylamine ([α] + = 20 -34.0 ° (without solvent)) under nitrogen atmosphere and add 3, 0 g of catalyst prepared as described under Method b.

The resulting mixture is stirred for 5 hours at 30 ° C. After filtration of the catalyst, the filtrate is distilled under reduced pressure to give 43.9 g of racemic ct- (p-tolyl) ethylamine. Boiling point 100-25 102 ° C / 17 mm Hg, [a] p ^ = -0.3 ° (without solvent).

EXAMPLE 5 EXAMPLE In a 50 ml flask, 20.0 g of (-) - α-phenyl- (5- (p-tolyl) ethylamine (["] q = -12.5 ° (without solvent)) is placed under a nitrogen atmosphere and 3.5 g of catalyst prepared as described under Method 5 are added. The mixture is stirred at 20 ° C. The optical rotation of the reaction mixture, measured during the reaction time, is shown in Table II below:

Table 11 2 5

Reaction time, [α] C Cu₂ (a solution of 10 hours of agent) 0 -12.5 ° 1 -10.9 ° 2 -5.8 ° 3 -2.6 ° 5 -1.2 ° 7 -0, 6 °

After filtration of the catalyst, the filtrate is distilled under reduced pressure to give 16.0 g of racemic α-phenyl-3- (p-tolyl) ethylamine.

Boiling point 132-133 ° C / 1.5 mm Hg, nj 2 = 1.5668.

EXAMPLE 6 Into a 100 ml flask is placed 20 g of (-) - α-phenyl-5- (p-tolyl) ethylamine 2.5 ([a] p = -8.5 ° (without solvent)) and 30 g of dry toluene under nitrogen atmosphere and 4.0 g of catalyst prepared as described under Method c are added. The mixture is stirred for 7 hours at 20 ° C.

After filtration of the catalyst, toluene is distilled off from the filtrate and the residue is distilled off under reduced pressure to give 17.5 g of racemic α-phenyl-p- (p-tolyl) ethylamine. Boiling point 120-124 ° C / 0.2 mm 25

Hg, [o] p = -0.3 ° (without solvent).

EXAMPLE 7 In a 50 ml flask, place 50 g of Lp-phenylalanine methyl ester ([a] q = +27.60 (c = 1 in ethanol)) under nitrogen atmosphere and add 3.7 g of catalyst prepared as described. under Method a. The mixture is stirred at 25 ° C. The optical rotation of the reaction mixture, measured during the reaction time, is shown in Table III below:

Table III 2 5

Reaction time, [α] min (c = 1, in ethanol) 10 + 0 + 27.6 ° 30 + 22.3 ° 60 + 16.1 ° 120 + 8.3 ° 160 + 3.5 ° 240 + 0.3 °

After filtration of the catalyst, the filtrate is distilled to give.

42.5 g racemic β-phenylalanine methyl ester, boiling point 90-92 ° C / 0.3 mm

Hg, [ct] p = + 0.2 ° (without solvent).

EXAMPLE 8 Into a 25 ml flask is placed 12.0 g of L-leucine ethyl ester under a nitrogen atmosphere and 1.8 g of catalyst prepared as described under Method b is added. The mixture is stirred for 5 hours at 20 ° C.

After filtration of the catalyst, the filtrate is distilled under reduced pressure to give 10.3 g of racemic leucine ethyl ester. Boiling point 9 n 83-84 ° C / 12 mm Hg, Mq = + 0.3 ° (without solvent).

EXAMPLE 9. In a 25 ml flask, place 10 g of L-aspartic acid diethyl ester ([α] p = -9.5 ° (without solvent)) under a nitrogen atmosphere and 1.7 g of catalyst prepared as described under Method a. The mixture is stirred for 3 hours at 25 ° C. After filtering off the catalyst, distill off. the filtrate under reduced pressure to give 9.0 g of racemic diethylaspartate. Boiling point 85-86 ° C / 1.0 mm Hg, = 5 -0.4 ° (without solvent).

EXAMPLE 10 2 In a 100 ml flask, place 20 g of L-8-phenylalanine methyl ester ([+] q = + 22.3 ° (without solvent)) and 20 g of dry toluene under nitrogen atmosphere and add 2.0 g of catalyst, prepared as described in Method a. The mixture is stirred for 5 hours at 30 ° C. After filtration of the catalyst, the toluene is distilled off and the solution obtained as the residue is distilled off under reduced pressure to give 17.0 g of racemic β-phenylalanine methyl ester. Boiling point 90-92 ° C / 0.3 mm 2 5

Hg, [α] p = + 0.3 ° (without solvent).

Part II

In this section examples of racemization are given using catalyst B.

EXAMPLE 11 In a flask of 25 ml, place 10 g of (-) - cc-phenylethylamine ([oc] q = -39 ° 20 (without solvent)) under a nitrogen atmosphere and add 0.2 g of 40% sodium dispersion in liquid paraffin. The mixture is stirred for 5 hours at 25 ° C. Then, a small amount of ethanol is added to the reaction mixture, deactivating the catalyst. After addition of water, the resulting mixture is extracted with toluene. The toluene extract is concentrated and distilled under reduced pressure to give 8.8 g of racemic α-phenylethylamine. Boiling point 105-107 ° C / 53 mm η c

Hg, [α] D = -0.2 ° (without solvent), n + = 1.5253.

2 O

EXAMPLE 12 In a 25 ml flask, place 10 g of L-alanine ethyl ester ([α] + = 2.3 ° (without solvent)) under a nitrogen atmosphere and add 0.15 g of 40% sodium dispersion in liquid paraffin. The mixture is stirred for 3 hours at 27 DEG C. Then the reaction mixture is treated as described in Example 11 to give 8.7 g of racemic alanine ethyl ester.

Island Island

Boiling point 48-52 ° C / 20 mm Hg, [α] D = 0 ° (without solvent).

EXAMPLE 13 Into a 25 ml flask, place 10 g of (-) - & - phenyl-α- (p-tolyl) ethylamine 2.5 (["] q = ~ 8.7 ° (without solvent)) under a nitrogen atmosphere and 0.2 g of 40% sodium dispersion in liquid paraffin is added. The mixture is stirred for 6 hours at 35 ° C. Then, the reaction mixture is treated as described in Example 11 to give 9.2 g of racemic 3-phenyl-α- (p-tolyl) ethylamine. Boiling point 107-109 ° C / 0.07 mm Hg, 15 = "0.1 ° (without solvent), n" = 1.5711.

Part III

In this section, examples of racemization are given using catalyst C.

EXAMPLE 14 20 Into a 25 ml flask, place 10 g of (+) - α- (1-naphthyl) ethylamine ([a] + = + 81.3 ° (without solvent)) under a nitrogen atmosphere and add 0.1 g of sodium -potassium alloy (Na: K = 56:44 by weight).

The mixture is stirred for 3 hours at 20 ° C. The reaction mixture is treated as described in Example 11 to give 9.3 g of racemic α- (1-25 naphthyDethylamine. Boiling point 124-126 ° C / 2.0 mm Hg. [A] + = -0.2 ° (without solvent) .

EXAMPLE 15 In a 25 ml flask, place 10 g of (+) - α, β-diphenylethylamine ([«] q = + 13.4 ° (without solvent)) under nitrogen atmosphere and add 0.1 g of sodium -potassium alloy (Na: K = 56:44 by weight).

The mixture is stirred for 2 hours at 25 ° C. The reaction mixture is treated as described in Example 11 to give 9.5 g of racemic α, β-diphenylethylamine. Boiling point 114-116 ° C / 0.3 mm Hg, [α] D = + 0.1 ° C (without solvent), n + = 1.5770.

EXAMPLE 16 In a 100-ml flask, 50 g of (+) - cc-phenyl- [3- (p-tolyl) ethylamine] ([“] q = + 12.5 ° (without solvent)) is placed under a nitrogen atmosphere. and 0.2 g of sodium potassium alloy is added (Na: K = 56:44 by weight). The resulting mixture is stirred for 5 hours at 25 ° C. The reaction mixture is treated as described in Example 11 to give 46.9 g of racemic α-phenyl-p- (p-tolyl) ethylamine. Boiling point 121-124 ° C / - 0.2 mm Hg, [α] D = + 0.2 ° (without solvent).

EXAMPLE 17 Into a 25 ml flask is placed 13.0 g of D-O-phenylalanine ethyl ester under a nitrogen atmosphere and 0.1 g of sodium potassium alloy 20 is added (Na: K = 56:44 by weight). The mixture is stirred for 3 hours at 20 ° C.

The reaction mixture is treated as described in Example 11 to give 12.1 g of racemic (5-phenylalanine ethyl ester, bp 95-96 ° C / 0.6 mm 5 mm Hg, [cc] + = -0.1 ° (without solvent).

Experiment 1.

(1) In a 100 ml flask, 50.0 g of (-) - α-phenylethylamine ([+] q = -39.9 ° (without solvent)) was placed under a nitrogen atmosphere and 0.125 g of metallic sodium was added thereto. The resulting mixture was heated under reflux (188 ° C) for 60 minutes. The optical rotation of the reaction mixture was measured to confirm its complete coincidence with the optical rotation of the starting compound.

Then 0.125 g of metallic sodium was again added to the reaction mixture and refluxing continued for approx. 20 minutes, during which a change to a dark red color was observed. The reaction mixture was cooled and distilled to give 17.0 g of α-phenylethyl-20 amine as a main fraction, boiling point 82-84 ° C / 12 mm Hg, [α] D = -0.01 ° (without solvent). Yield 34.0%. 21.3 g of the residue were obtained.

(0) 20.0 g of (-) - α-phenylethylamine ([a] q = -39.9 ° (without solvent)) was placed in a 50 ml flask under nitrogen atmosphere and 0.5 g of metallic was added. sodium. The mixture was reacted at 60 ° C for 8 hours. A sample was taken from the reaction mixture and the optical rotation measured, which showed a coincidence with the optical rotation of the starting compound. Thus, no racialization took place.

(3) 20.0 g of (-) - α-phenyl-β- (p-tolyl) -2-ethylamine ([α] D = -12.0 ° (without solvent)) was placed under nitrogen in a 50 ml flask atmosphere and 0.5 g of metallic sodium was added. The resulting mixture was heated at 80 ° C for 20 hours, and the reaction mixture showed an optical rotation of [α] D = -6.2 ° (without solvent), forming as an by-product an unidentified substance in a yield. of 41%. After elimination of the by-product, the optical rotation of the residual product was [α] + = -11.3 ° (without solvent).

(4) Into a 50 ml flask were placed 20.0 g of (-) - α-phenyl-fJ- (p-tolyl) -2 ethylamine ([a] p = -12.0 ° (without solvent)) under nitrogen atmosphere and 0.5 g of metallic sodium was added. The resulting mixture was stirred at 60 ° C for 10 hours. No change in optical rotation was observed.

Experiment 2.

In a 50 ml flask 20.0 g of (-) - a-phenylethylamine ([o] qj =

-39.9 ° (without solvent)). Racemization was performed at 20 ° C

And (3.0 g), (2) 40% Na dispersion in liquid paraffin (0.4 g) or (3) sodium potassium alloy (Na: K = 56:44) (0.2 g) as catalyst. The results are shown in Table IV below:

Table IV

Catalyst Reaction Conditions Results ——

Temperature Time Yield [α] +, ° C (h) Tea (%) (1) 10 _: _: _. (1) 10% Na-Al2Og (3.0 g) 20 8 92.4 -0.1 ° (2) 40% Na dispersion in liquid paraffin (0.4 g) 20 7 92.0 -0 , 2 ° (3) Na-K alloy (0.2 g) 93.5 -0.2 ° 15 without solvent